Camptodactyly in Sotos syndrome

We describe a girl with Sotos syndrome presenting at two and a half years age with developmental delay. She has camptodactyly which has not previously been reported in Sotos syndrome but is a common finding in Weaver syndrome. Both these conditions have been reported to have NSD1 gene mutations. This report is consistent with the conditions being allelic.     

Hantaviruses: an emerging public health threat in India? A review

The emerging viral diseases haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are a cause of global concern as they are increasingly reported from newer regions of the world. The hantavirus species causing HFRS include Hantaan virus, Seoul virus, Puumala virus, and Dobrava-Belgrade virus while Sin Nombre virus was responsible for the 1993 outbreak of HCPS in the Four Corners Region of the US. Humans are accidental hosts and get infected by aerosols generated from contaminated urine, feces and saliva of infected rodents. Rodents are the natural hosts of these viruses and develop persistent infection. Human to human infections are rare and the evolution of the virus depends largely on that of the rodent host. The first hantavirus isolate to be cultured, Thottapalayam virus, is the only indigenous isolate from India, isolated from an insectivore in 1964 in Vellore, South India. Research on hantaviruses in India has been slow but steady since 2005. Serological investigation of patients with pyrexic illness revealed presence of anti-hantavirus IgM antibodies in 14.7% of them. The seropositivity of hantavirus infections in the general population is about 4% and people who live and work in close proximity with rodents have a greater risk of acquiring hantavirus infections. Molecular and serological evidence of hantavirus infections in rodents and man has also been documented in this country. The present review on hantaviruses is to increase awareness of these emerging pathogens and the threats they pose to the public health system.     

Hypoparathyroidism-retardation-dysmorphism syndrome

Congenital hypoparathyroidism, growth retardation and facial dysmorphism is a rare autosomal recessive disorder seen among children born to consanguineous couple of Arab ethnicity. This syndrome is commonly known as Sanjad-Sakati or hypoparathyroidism-retardation-dysmorphism syndrome (HRD). We report 13-year-old Hindu boy with hypoparathyroidism, tetany, facial dysmorphism and developmental delay, compatible with HRD syndrome.     

Tratamiento y evolución del síndrome de tormenta de citoquinas asociados a infección por SARS-CoV-2 en pacientes octogenarios

IntroductionCytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution.Patients and methodRetrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival.Results21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8 mg/dL (22-306) and D-dimers 2.9 m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925 microg/L; P = .045) and CRP (197.6 vs. 76 mg / dL; P = .007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727 microg/L, CRP of 27 mg/dl and D-dimers of 1.18 mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments.ConclusionsSTC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.     

A patient with hydranencephaly and PEHO-like dysmorphic features

Progressive encephalopathy with Edema, Hypsarrhythmia, and Optic atrophy (PEHO syndrome) is a rare recessive autosomal neurodegenerative condition essentially described in Finland. The term PEHO-like syndrome has been proposed for patients who share clinical features of PEHO syndrome but lack the cerebellar atrophy, one of its major diagnostic criteria. We describe a patient presenting with hypoxic-ischaemic encephalopathy and PEHO-like syndrome features.     

Escobar syndrome in three male patients of same family

We describe three male individuals from a consanguineous south Indian family affected with the multiple pterygium syndrome (Escobar syndrome). Common clinical features included short stature, multiple pterygium, skeletal anomalies, and normal intelligence. The first report of this condition was made in 1902 from this same place (Pondicherry) and the disease received its present popular name Escobar syndrome in 1982. The genetic defect for this condition was identified in 2006 as mutation in the fetal acetylcholine receptor.     

The genomic sequence for Prader-Willi/Angelman syndromes' loci of human is apparently conserved in the great apes

Chromosomal changes through pericentric inversions play an important role in the origin of species. Certain pericentric inversions are too minute to be detected cytogenetically, thus hindering the complete reconstruction of hominoid phylogeny. The advent of the fluorescence in situ hybridization (FISH) technique has facilitated the identification of many chromosomal segments, even at the single gene level. Therefore the cosmid probe for Prader-Willi (PWS)/Angelman syndrome to the loci on human chromosome 15 [ql 1-12] is being used as a marker to highlight the complementary sequence in higher primates. We hybridized metaphase chromosomes of chimpanzee (PTR), gorilla (GGO), and orangutan (PPY) with this probe (Oncor) to characterize the chromosomal segments because the nature of these pericentric inversions remains relatively unknown. Our observations suggest that a pericentric inversion has occurred in chimpanzee chromosome (PTR 16) which corresponds to human chromosome 15 at PTR 16 band pl 112, while in gorilla (GGO 15) and orangutan (PPY 16) the bands q11-12 complemented to human chromosome 15 band q11-12. This approach has proven to be a better avenue to characterize the pericentric inversions which have apparently occurred during human evolution. Genetic divergence in the speciation process which occurs through chromosomal rearrangement needs to be reevaluated and further explored using newer techniques.Correspondence to: R.S. Verma     

Radiobiology of the acute radiation syndrome

Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. The time course and severity of clinical signs and symptoms are a function of the overall body volume irradiated, the inhomogeneity of dose exposure, the particle type, the absorbed dose and the dose rate. Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. Contemporaneously, many other radiation-induced effects has been described and all of them may lead to tissue injury with their corresponding signs and symptoms that can be expressed after short or long period of time. Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines.     

Duane anomaly, congenital myopathy and severe scoliosis in sibs: new AR syndrome?

We report on two sisters who show a similar pattern of anomalies consisting of bilateral Stilling-Türk-Duane retraction syndrome (type 3), non-progressive hypotonia with delayed motor milestones but normal intelligence, severe, early onset scoliosis, and short stature. Muscular biopsy revealed numerous regenerating fibers, but no specific abnormalities among the non-regenerating fibers. This combination of anomalies has not been previously reported, and could represent a new autosomal recessive syndrome. The only differential diagnosis is Crisfield-Dretakis-Sharpe syndrome, a combination of lateral gaze palsy, ptosis, and scoliosis without hypotonia, recessively inherited.     

Comparative study of normal, Crouzon, and Apert craniofacial morphology using finite element scaling analysis

Finite element scaling analysis is used to study differences in morphology between the craniofacial complex of normal individuals and those affected with the syndromes of Apert and Crouzon. Finite element scaling quantifies the differences in shape and size between forms without reference to any fixed, arbitrary registration point or orientation line and measures the amount of form change required to deform one object into another. Two-dimensional coordinates of landmarks digitized from annual sets of cephalometric radiographs were used in the analysis. A simple tabulation shows no difference in variances between the normal and pathological samples. A test of mean differences depicts the Apert and Crouzon morphologies as significantly different from normal. The Apert palate differs from normal in shape in the older age groups analyzed, and palatal size differences are most common at the posterior nasal spine. The Apert pituitary fossa and basi-occiput are significantly larger than normal. The Crouzon pituitary fossa is also larger than normal, but the difference is not always significant. The typical morphology of the Crouzon nose is due more to differences in shape than size. The Crouzon basi-occiput is significantly smaller than normal. An age association of the differences between the normal and pathological craniofacies was found in Apert syndrome but not in Crouzon syndrome. Apert syndrome is characterized by a more homogeneous pattern of craniofacial dysmorphology from 6 months to 18 years of age than Crouzon syndrome.     

不同证型多囊卵巢综合征患者的临床和生化特征研究

目的:探讨"痰湿证"和"非痰湿证"多囊卵巢综合征(Polycystic ovary syndrome,PCOS)患者的临床和生化特征。方法:纳入PCOS患者89例(其中痰湿证42例、非痰湿证47例)及正常对照52例(其中痰湿证对照组21例、非痰湿证对照组31例),采集和比较其临床资料及血清糖脂代谢指标、性激素水平的差异。结果:PCOS患者月经初潮年龄明显晚于正常对照组,两种证型PCOS患者均存在临床表现、性激素、糖代谢、脂代谢的异常,表现在多毛评分、黑棘皮、皮肤溢脂、痤疮发生率明显高于对照组;黄体生成素((Luteinizing hormone,LH)、黄体生成素/促卵泡激素(Follicle stimulating hormone,FSH)、雌二醇(Estradiol,E2)、睾酮(Testosterone,T)、游离雄激素指数(Free androgen index,FAI)、空腹葡萄糖(Fast blood glucose,FBG)、甘油三酯(Triglyceride,TG)水平明显高于对照组;高密度脂蛋白(High density lipoprotein,HDL)水平显著低于对照组(P0.05)。而"痰湿型"PCOS以体重指数(Body mass index,BMI)、腰臀比(Waist hip ratio,WHR)、收缩压、黑棘皮和皮肤溢脂发生率、FAI、FBG、空腹胰岛素(Fast Insuline,FINS)、稳态模型胰岛素抵抗指数(Homeostasis model insulin resistance index,HOMA-IR)水平增高为主;而"非痰湿型"PCOS以LH/FSH、LH水平增高为主;与"非痰湿"对照组相比,"痰湿"对照组BMI、WHR、收缩压、FBG、TG、低密度脂蛋白(Low density lipoprotein,LDL)、HOMA-IR明显升高。结论:"痰湿证"PCOS患者以糖脂代谢异常和胰岛素抵抗为主,而"非痰湿证"PCOS患者以性腺轴紊乱和高雄激素血症为主,将PCOS患者分为"痰湿证"和"非痰湿证",能反映疾病不同证型的基本特点,对远期并发症的防治有指导意义。     

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions.     

Concurrence of fragile X and Klinefelter syndromes: report of a new case of paternal nondisjunction

The concurrence of fragile X and Klinefelter syndromes would be expected occasionally. Therefore, the analysis of the literature showed that the concurrence of both conditions was found at least 16 times. Among them, only seven cases were analyzed for the parental origin of the extra chromosome X, suggesting that the maternal nondisjunction was preferentially inherited. We present the third patient with the concurrence of fragile X and Klinefelter syndromes, in which the parental origin of the supernumerary chromosome X was paternal. This finding reinforces that the parent-of-origin predisposition of the concurrence of the fragile X and Klinefelter syndromes is a pure coincidence.     

Ross operation in a neuro-cardio-facial-cutaneous syndrome patient

Congenital heart diseases are a major part of Costello and cardio-facio-cutaneous syndromes. Subaortic stenosis was reported rarely and Ross operation never in these syndromes.We reported a girl patient whose manifestations were consistent with these syndromes. Distinction between these syndromes was not possible as genetic testing was not carried out. She developed severe neoaortic regurgitation 2.5 years after the Ross operation and died due to the complications of aortic valve replacement.Ross operation may be an unsuitable option in these syndromes due to the possibility of subtle pulmonic valve pathology.     

Leptospirosis and Goodpasture's Syndrome: Is there an etiological link?

Renal and pulmonary dysfunctions are common in both leptospirosis and Goodpasture's Syndrome. While leptospires are the etiological agents of leptospirosis, they may also be etiological agents for Goodpasture's Syndrome.     

Double trisomy (48,XXY,+21) in monozygotic twins: case report and review of the literature

The occurrence of double aneuploidy in the same individual is a relatively rare phenomenon. We describe twin newborns with typical clinical features of Down's syndrome, of which one revealed 48,XXY,+21 GTG-band karyotype. The second newborn died 2 days after its birth, and was clinically diagnosed having Down syndrome. Due to the same clinical features of the twins, the common placenta and amniotic sac, we speculate that they were monozygotics and as a result the second newborn should also be a Klinefelter. The purpose of this report is to present a rare case of possible coincidence of double aneuploidy in newborn twins. A review of the literature showed that double trisomy (48,XXY,+21) in a twin newborn infant has never occurred.     

中医热证实质研究

目的本文对我们以往热证实质研究课题的临床及实验研究成果进行了初步汇总,以期为中医热证本质研究、热证虚实辨证及热证动物模型研究提供更加充分的理论及实验依据。方法本研究从物质及能量代谢角度出发,重点考察热证不同状态（实热证、虚热证）下,甲状腺激素水平、甲状腺超微结构、肝细胞超微结构、肝细胞线粒体立体形态计量以及肝细胞线粒体琥珀酸脱氢酶活性,同时进行了中药疗效观察。结果虚热证的产生可能与甲状腺激素有关,而实热证可能与之无关。实热证、虚热证模型大鼠机体能量代谢都比较旺盛,机体产能和耗能增加,但实热证不如虚热证变化显著,且二者病理基础不同。清热解毒、滋阴清热中药对热证状态下大鼠的各项病理改变具有一定保护作用。结论根据研究结果推断血清T3、T4、rT5、TSH和甲状腺超微结构改变可作为中医热证虚、实辨证的有效指标。热证与机体能量代谢变化趋势呈正相关。     

Molecular Analysis of Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) Deficiencies: Novel Mutations and the Spectrum of Japanese Mutations

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase, (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. We have identified a number of HPRT mutations in patients manifesting different clinical phenotypes, by analyzing all nine exons of the HPRT gene (HPRT1) from genomic DNA and reverse transcribed mRNA using the PCR technique coupled with direct sequencing. Recently, we detected two novel mutations: a single nucleotide substitution (430C > T) resulting in a nonsense mutation Q144X, and a deletion of HPRT1 exon 1 expressing no mRNA of HPRT. Furthermore, we summarized the spectrum of 56 Japanese HPRT mutations.